PMID- 20075159
OWN - NLM
STAT- MEDLINE
DCOM- 20100413
LR  - 20211020
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 115
IP  - 11
DP  - 2010 Mar 18
TI  - Genetic variations in the heparanase gene (HPSE) associate with increased risk of 
      GVHD following allogeneic stem cell transplantation: effect of discrepancy 
      between recipients and donors.
PG  - 2319-28
LID - 10.1182/blood-2009-08-236455 [doi]
AB  - Graft-versus-host disease (GVHD) is the most common cause of nonrelapse mortality 
      and morbidity after hematopoietic stem cell transplantation (HSCT). The 
      well-documented involvement of heparanase in the process of inflammation and 
      autoimmunity led us to investigate an association between HPSE gene 
      single-nucleotide polymorphisms (SNPs) and the risk of GVHD. The present study 
      indicates a highly significant correlation of HPSE gene SNPs rs4693608 and 
      rs4364254 and their combination with the risk of developing acute GVHD. Moreover, 
      the study revealed that discrepancy between recipient and donor in these SNPs may 
      elevate significantly the risk of acute GVHD. This association was statistically 
      significant when the recipients possessed genotype combinations dictating higher 
      levels of heparanase compared with their human leukocyte antigen (HLA)-matched 
      donors. In addition, HPSE gene SNPs disclosed a correlation with extensive 
      chronic GVHD, nonrelapse mortality, and overall survival. Our study indicates 
      involvement of heparanase in the development of acute and extensive chronic GVHD. 
      Moreover, it suggests a possible mechanism for the aggressive behavior of T 
      lymphocytes leading to GVHD when the recipients possess genotype combinations 
      that dictate high levels of heparanase mRNA compared with their HLA-matched 
      donors expressing low levels of heparanase.
FAU - Ostrovsky, Olga
AU  - Ostrovsky O
AD  - Laboratory of Molecular Immunobiology, Department of Hematology and Bone Marrow 
      Transplantation, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
FAU - Shimoni, Avichai
AU  - Shimoni A
FAU - Rand, Avital
AU  - Rand A
FAU - Vlodavsky, Israel
AU  - Vlodavsky I
FAU - Nagler, Arnon
AU  - Nagler A
LA  - eng
GR  - R01 CA106456/CA/NCI NIH HHS/United States
GR  - R01-CA106456/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100114
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - EC 3.2.1.- (heparanase)
RN  - EC 3.2.1.31 (Glucuronidase)
SB  - IM
MH  - Acute Disease
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Chronic Disease
MH  - Female
MH  - Gene Frequency/genetics
MH  - *Genetic Predisposition to Disease
MH  - Glucuronidase/*genetics
MH  - Graft vs Host Disease/*enzymology/*genetics/prevention & control
MH  - *Hematopoietic Stem Cell Transplantation/mortality
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Multivariate Analysis
MH  - Polymorphism, Single Nucleotide/*genetics
MH  - Recurrence
MH  - Survival Analysis
MH  - *Tissue Donors
MH  - Transplantation Conditioning
MH  - Transplantation, Homologous
MH  - Young Adult
PMC - PMC2844015
EDAT- 2010/01/16 06:00
MHDA- 2010/04/14 06:00
PMCR- 2011/03/18
CRDT- 2010/01/16 06:00
PHST- 2010/01/16 06:00 [entrez]
PHST- 2010/01/16 06:00 [pubmed]
PHST- 2010/04/14 06:00 [medline]
PHST- 2011/03/18 00:00 [pmc-release]
AID - S0006-4971(20)56643-3 [pii]
AID - 2009/236455 [pii]
AID - 10.1182/blood-2009-08-236455 [doi]
PST - ppublish
SO  - Blood. 2010 Mar 18;115(11):2319-28. doi: 10.1182/blood-2009-08-236455. Epub 2010 
      Jan 14.